In one collaborative study, we assessed the diagnostic performance and clinical utility of various thyroid function tests in 135 patients with central (secondary and tertiary) hypothyroidism. As expected, we found that, in contrast to patients with pri-mary hypothyroidism, measurement of thyrotropin (thyroid stimulating hormone) cannot be used to assess the clinical thyroid status in central hypothyroid patients. Determination of free thyroxine with analytically sound and clinically validated methods usually was reli-able for guiding levothyroxine replacement therapy in these patients. In another study, we developed a new approach using quantitative research synthesis for assessing the effects of thyrotropin suppression by thyroid hormones on benign solitary thyroid nodules. This approach involved systematic review of the literature for clinical studies and expert opinions, meta-analysis of selected interventional studies, survey of NIH endocrinology practitioners for therapeutic decisions in hypothetical patients with benign solitary thyroid nodule, prac-tice validation in NIH patients treated with levothyroxine suppression for benign solitary thyroid nodules, and application of Hills criteria to assess causality between thyroid sup-pression therapy and regression of benign solitary thyroid nodules. We concluded that since approximately one-quarter of patients with benign solitary thyroid nodule may respond with a clinically significant (>50 percent) reduction in nodule size to levothyroxine suppression therapy, an initial trial of this therapy is warranted in all of these patients in the absence of contraindication(s) to levothyroxine administration. In other studies now in progress we are assessing the clinical utility of thyrotropin sup-pression by thyroid hormones in patients with multinodular goiter, further, we are studying the effects of various blood collection tubes on the measurements of free thyroxine and thyrotropin thyroid stimulating hormone with different non-isotopic methods.